The NSABP has randomized more than 100,000 patients with diagnoses of breast or colorectal cancers into clinical trials during the past 50 years. Based on incremental benefit achieved through multiple evolutionary steps of treatment modalities tested in those trials, significant improvement in patient outcomes has been achieved overall. However, this approach also means that there has been significant over-treatment of some patients who did not benefit from the various interventions, which now have become part of legacy treatments to which newer agents are added. Development of reliable prognostic and predictive tests is required to deliver the goal of more personalized treatment. Since, for ethical reasons, trials cannot be conducted again once the efficacy of newer regimens is demonstrated, archived tumor tissue blocks from historical trials conducted by the NSABP provide an essential resource to investigators who are trying to develop such tests. The NSABP Biospecimen Bank at the NSABP Division of Pathology Tissue Bank houses tumor-tissue specimens from more than 87,000 patients and serves as an open resource to the scientific community to provide tissues for development and clinical validation of new prognostic or predictive tests. Tissue specimens are provided to investigators from both academia and the private sector on the basis of scientific merit. A multi-gene expression based prognostic test (OncotypeDx) developed in a collaboration between the private sector and the bank has become a standard in clinical management of hormone receptor positive node negative breast cancer in the United States. In-house development and/or optimization of methods for whole-genome gene-expression analyses and mutation profiling of formalin-fixed, paraffin-embedded blocks further enhances the value of the NSABP Biospecimen Bank.